ABSTRACT COVID-19 is a severe respiratory tract infection caused by the newly discovered, and highly contagious, SARS- CoV-2 virus that emerged in late 2019 in Wuhan, China and has infected over 3 million people globally (> 1M US) and has caused over 215,000 deaths (58,000 US). SARS-CoV-2 RNA is the only sensitive and specific biomarker for diagnosis of an active COVID-19 infection and is diagnosed by reverse-transcription polymerase chain reaction (RT-PCR) in a central virology lab. Several CLIA-waived NAAT systems have been rapidly adapted for testing COVID-19, and have been granted the Emergency Use Authorization (EUA) for use at the point-of-care; however, their use is generally restricted to clinical sites because of the instrument, and/or protocol complexity, and high cost associated with the equipment. Self-administered nasal swabs have been shown to be an effective sample to detect COVID-19, and as a result the FDA is allowing their use as an acceptable specimen for COVID-19 laboratory testing, paving the way for home-based COVID NAT tests. We currently have a NIBIB project focused on the development and validation of a paper microfluidic based POC NAT for quantifying HIV Viral load from whole blood. Here, we propose to leverage this on-going effort to develop a COVID-19 Nucleic Acid Amplification Self Test (COAST) that can be performed at home to detect COVID-19 infections based on SARS-CoV-2 RNA. COAST is fully disposable test will detect as little as 5,000 cp/swab, have a COGS of less than $2.50, and will have sample-to-result within 30 minutes. In this proposal, our primary objectives are (1) optimizing and validating a sensitive and specific Recombinase Polymerase Amplification (RPA) isothermal amplification assay for the N-gene for SARS-CoV-2 RNA with lateral flow readout and (2) developing and evaluating the COAST home-based test with integrated sample preparation, isothermal amplification, lateral flow read-out. RPA is a low-temperature, isothermal amplification chemistry that can specifically detect a target with a wide range of genomic diversity and easily be integrated with LFA read-out. COAST has a novel elution tube, self-regulating positive temperature coefficient heaters, on-paper RPA amplification, and LFA readout. The RPA assay will be validated with de-identified SARS-CoV-2 RNA from COVID-19 patient samples collected by UWs Virology Lab and the COAST cartridge will be evaluated using mock nasal swabs with non-infectious targets. COVID-19 self-testing can drastically increase total testing numbers which can improve state and federal public health officials understanding of disease proliferation, as well as informing policy response (e.g. stay-at-home orders, school closures, etc.) and allocation of emergency response (for example distribution of PPE or ventilators). Self-testing can also reduce new infections by initiating prompt quarantine and public health contact tracing, especially in the case of asymptomatic or mildly symptomatic patients.